Prevalence of Hepatitis Delta Infection in the United States: National Health and Nutrition Examination Survey, 1999-2012

To the Editor

Hepatitis delta virus (HDV) is a defective RNA virus requiring acute or chronic hepatitis B viral coinfection.¹ The prevalence of HDV in the US general population is currently unknown, though a relatively high seroprevalence of 3.4% was reported among hepatitis B surface antigen-positive US veterans.² Previous small studies involving hepatitis B surface antigen-positive patients have also revealed high HDV prevalence rates among injection drug users (11%), hemophiliacs (19%), and men who have sex with men (2%).^3-5

We used National Health and Nutrition Examination Survey data (1999-2012) to obtain estimates of HDV prevalence for the US population using weighted samples. In the National Health and Nutrition Examination Survey, the test for antibody to HDV is performed on participants with a positive test for hepatitis B core antibody and hepatitis B surface antigen. We calculated sample proportions to determine HDV period prevalence. We stratified estimates by gender, race, human immunodeficiency virus hepatitis C virus coinfections, injection drug use, and sexual behavior.

From 1999 to 2012, data on 71,916 individuals were obtained, with 52,209 (72.6%) receiving HDV testing. The overall prevalence of HDV in the United States was 0.02% (10/52209), with a mean age of 52.1 ± 14.0 years and 60% males. Table 1 summarizes our results.

Table 1. Patient Demographics and Clinical Characteristics Stratified by HDV Status.

Variable	HDV-Negative, % (n = 52,199)	HDV-Positive (%) (n = 10)	P
Mean age, years (SD)	36.6 (23.01)	52.1 (14.01)	0.02
Sex
Male	49.2	60.0	0.54
Female	50.8	40.0
Race/ethnicity
Mexican American	23.3	10.0	0.01
Other Hispanic	7.1	0
Non-Hispanic white	40.3	10.0
Non-Hispanic black	23.3	50.0
Other race, including multiracial	6.0	30.0
HCV antibody
Positive	1.2	20	0.08
Negative	98.8	80
HIV status
Positive	0.5	20	0.03
Negative	99.5	80
Injection drug use
Yes	2.8	0	0.99
No	97.2	100
Homosexual men
Yes	5.2	25	0.19
No	94.8	75

Fisher's exact test was used for categorical variables and the Mann-Whitney test for continuous variables.

Abbreviations: HCV, hepatitis C virus; HIV, human immunodeficiency virus; SD, standard deviation.

The prevalence of HDV in the United States is significantly lower than previously reported. Compared to veteran population estimates, the prevalence of HDV is more than 100-fold less common among the civilian US population with chronic hepatitis B infection. This study is limited by the likelihood of this data set to underestimate the true prevalence owing to exclusion of high-risk populations such as the homeless, incarcerated, and institutionalized, in whom high-risk characteristics (e.g., injection drug use) are overrepresented.

Despite these limitations, this study represents the first report attempting to establish an estimate of the prevalence of HDV in the general US population. Routine screening for HDV in hepatitis B virus-infected patients and the general population is not presently supported by available evidence, although future research will be required to further define key at-risk populations for whom risk factor-based testing may be indicated.